Gene expression association study in feline mammary carcinomas

Ferreira, Daniela; Martins, Berta; Soares, Maria Carolina S.; Correia, Jorge; Adega, Filomena; Ferreira, Fernando; Chaves, Raquel

doi:10.1371/journal.pone.0221776

Cited by 11 publications

(7 citation statements)

References 60 publications

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“…Feline mammary carcinoma (FMC) is a high prevalence disease (12–40% of all tumors in cat) that shows similar clinicopathological and genetic features ( 1 ), comparing to human breast cancer ( 2 ), supporting its use in comparative oncology studies ( 3 , 4 ), and allowing to improve therapeutic protocols for women and cats ( 5 ). Despite the cat is considered a suitable cancer model, especially for the most aggressive mammary carcinomas subtypes, HER2-positve ( 2 , 6 ) and triple-negative ( 6 – 8 ), further efforts are needed to track disease progression ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes

et al. 2021

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Obesity is an established risk factor for breast cancer in post-menopausal women, being associated with elevated serum levels of leptin. Although overweight is a common condition in cat, the role of leptin and its receptor in feline mammary carcinoma remains unsettled. In this study, serum leptin and leptin receptor (ObR) levels were investigated in 58 cats with mammary carcinoma and compared with those of healthy animals, as were the expression levels of leptin and ObR in tumor tissues. The results showed that the Free Leptin Index is significantly decreased in cats with mammary carcinoma (p = 0.0006), particularly in those with luminal B and HER2-positive tumors, and that these animals also present significantly lower serum leptin levels (p < 0.0001 and p < 0.005, respectively). Interestingly, ulcerating tumors (p = 0.0005) and shorter disease-free survival (p = 0.0217) were associated to serum leptin levels above 4.17 pg/mL. In contrast, elevated serum ObR levels were found in all cats with mammary carcinoma (p < 0.0001), with levels above 16.89 ng/mL being associated with smaller tumors (p = 0.0118), estrogen receptor negative status (p = 0.0291) and increased serum levels of CTLA-4 (p = 0.0056), TNF-α (p = 0.0025), PD-1 (p = 0.0023), and PD-L1 (p = 0.0002). In tumor samples, leptin is overexpressed in luminal B and triple-negative carcinomas (p = 0.0046), whereas ObR is found to be overexpressed in luminal B tumors (p = 0.0425). Altogether, our results support the hypothesis that serum levels of leptin and ObR can be used as biomarkers of specific feline mammary carcinoma subtypes, and suggests the use of leptin antagonists as a therapeutic tool, reinforcing the utility of the cat as a cancer model.

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Section: Introductionmentioning

confidence: 99%

Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes

et al. 2021

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“…One study found a significant association between ERBB2 RNA levels and tumour malignancy as well as molecular subtypes; higher ERBB2 expression correlated with lower malignancy grade and with the luminal A and HER2 subtypes, whereas the lowest ERBB2 levels correlated with the triple negative tumours [ 49 ]. Another study found that relative to disease-free tissue from the same cat, mammary carcinomas showed overexpression of several other cancer-associated genes, including CCND1 , PKM2 , PTBP1 and TOP2α , whilst levels of TP53 , c-MYC , YBX1 and FUS remained unchanged [ 52 ]. Interestingly, positive correlations were found between tumour size and YBX1 RNA levels, lymph node metastasis and c-MYC RNA levels [ 52 ].…”

Section: Mammary Tumoursmentioning

confidence: 99%

Feline Oncogenomics: What Do We Know about the Genetics of Cancer in Domestic Cats?

Ludwig

Dobromylskyj²,

Wood

et al. 2022

Veterinary Sciences

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Cancer is a significant cause of morbidity and mortality in domestic cats. In humans, an understanding of the oncogenome of different cancer types has proven critical and is deeply interwoven into all aspects of patient care, including diagnostics, prognostics and treatments through the application of targeted therapies. Investigations into understanding the genetics of feline cancers started with cytogenetics and was then expanded to studies at a gene-specific level, looking for mutations and expression level changes of genes that are commonly mutated in human cancers. Methylation studies have also been performed and together with a recently generated high-quality reference genome for cats, next-generation sequencing studies are starting to deliver results. This review summarises what is currently known of the genetics of both common and rare cancer types in cats, including lymphomas, mammary tumours, squamous cell carcinomas, soft tissue tumours, mast cell tumours, haemangiosarcomas, pulmonary carcinomas, pancreatic carcinomas and osteosarcomas. Shining a spotlight on our current understanding of the feline oncogenome will hopefully serve as a springboard for more much-needed research into the genetics of cancer in domestic cats.

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“…In order to surpass the limitations of laboratory rodents, the use of domestic animal models with spontaneous tumors has increased, allowing researchers to understand the tumorigenesis process [ 34 , 35 ]. Despite cats being considered a valuable human model for different diseases [ 3 , 36 , 37 ], efforts are needed for a deeper understanding of the FMC development, not only to improve cats’ survival time but also to reinforce its use as an oncology model.…”

Section: Introductionmentioning

confidence: 99%

VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes

Gameiro

Nascimento

Correia

et al. 2021

Cancers

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Feline mammary carcinoma (FMC) is a common neoplasia, showing aggressive clinicopathological features, without viable therapeutic options. The study of tumor microenvironment has gained importance, due to the ability to control tumor progression by regulating the immune response. Considering the lack of knowledge, feline serum VISTA levels from cats with mammary carcinoma were compared with healthy controls, and with serum levels of PD-1/PD-L1, CTLA-4, LAG-3, IL-6, and TNF-α. In parallel, VISTA tumor expression was evaluated in FMC samples. The obtained data revealed that serum VISTA levels were significantly higher in cats presenting HER2-positive (p = 0.0025) or triple-negative subtypes (p = 0.0019), with higher serum levels in luminal A (p = 0.0025) correlated to the presence of metastasis (p = 0.0471). Furthermore, in HER2-positive or triple-negative tumors, correlations were obtained between serum VISTA levels and the serum levels of the above-mentioned molecules. In tumors, VISTA expression revealed a stronger intensity in cancer cells, when compared to TILs (p < 0.0001). Stratifying the samples by subtypes, a higher number of VISTA-positive TILs was observed in the HER2-positive subtype, compared with triple-negative tumors (p = 0.0138). In conclusion, results support the development of therapeutic strategies for HER2-positive and triple-negative FMC subtypes, reinforcing the use of cats as a human oncology model.

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Gene expression association study in feline mammary carcinomas

Cited by 11 publications

References 60 publications

Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes

Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes

Feline Oncogenomics: What Do We Know about the Genetics of Cancer in Domestic Cats?

VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes

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